The binding of chemoattractant agents such as FMLP to specific cell surface receptors on human polymorphonuclear leukocytes (PMNS) initiates a variety of biologic responses, Including chemotaxis, release of superoxide anions, and lysosomal enzyme secretion. Chemoattractant receptors occupancy leads to the activation of phospholipase C, which results in the hydrolysis of PIP2 to IP3 and diacylglycerol. These products, through calcium mobilization and protein kinase C(PKC) activation initiate (cell activation.?) Chemoattractant binding also results in the rapid, transient increase in cellular cAMP. cAMP, formed via chemoattractant receptors and other cAMP mediated receptors, acts to terminate cell activation. It was purpose of this study to investigate the process leading to the formation of cAMP by chemoattractant receptors in leukocytes. The procedure for the precise measurement of cAMP levels in leukocytes was developed based on a RIA assay. The results show stimulation of cAMP formation by FMLP, and by PMA ( a tumor promoter agent and activator of PKC), as well as by an adrenergic agonist, isoproterenol (Iso). Propanolol (1 micro-M) inhibits cAMP production by Iso but has no effect on CAMP formation by either PMA or FMLP. Conversely, a specific inhibitor of PKC such as staurosporine inhibits cAMP formation in the presence of FMLP and PMA. The results indicate that the formation of cAMP by FMLP and PMA is through a PKC activation process. It has also been observed that the presence of adenosine potentiates the effect of FMLP and PMA on cAMP formation and this potentiation is abolished by addition of adenosine deaminase. Furthermore, other kinases such as calmodulin dependent kinase seem to play a role in this process, since the effect of adenosine is eliminated in the presence of trifluroparazine (calmodulin inhibitor). The results of this study are being prepared for publication.